This proposal uses the baboon as a model to investigate the role of neonatal overfeeding as a factor leading to adolescent obesity. The long term objective of this proposal is to determine the mechanism(s) by which neonatal overfeeding results in hypertrophic obesity in adolescent baboons. It is hypothesized that neonatal overfeeding metabolically programs an enhanced capability to store triglyceride in adipocytes and this ability is triggered by the onset of puberty. The objectives of this proposal are to test this hypothesis, identify physiological factors associated with neonatal overfeeding that may result in adipocyte hypertrophy, and to determine if hormones (T3, cortisol, and insulin) affected by neonatal overfeeding during the early infant period program increased triglyceride synthesis in preadipocytes in vitro. We will conduct in vivo studies with 22 baboons, previously overfed (n = 9) and normally fed (n = 13) as infants, as they enter puberty (4 to 6 years of age) to determine if neonatal overfeeding affects: 1) fat mass and adipocyte hypertrophy prior to or after puberty (Aim 1); 2) postprandial triglycerides, fat uptake into adipose tissue, and lipoprotein lipase activity (Aim 2); 3) total energy expenditure (Aim 3); 4) the length of the menstrual cycle and progesterone and estrogen plasma levels (Aim 4); 5) fasting and postprandial plasma insulin and cortisol levels, cortisol production, and thyroid hormone levels (Aim 5).